Tolvaptan effectively corrects Hyponatremia, but is correction too rapid?- Dr. Deepika Jain

Vaptans including tolvaptan is an extraordinary discovery in the management of hyponatremia. Hyponatremia is a very serious condition and commonly encountered in a hospital setting. Whether its acute or chronic hyponatremia, it makes a nephrologist lose their sleep over it. After many years, the vasopressin antagonists (vaptans) have been approved for use in both inpatient and outpatient settings.

In a recent study by Morris et al, they describe their experience with tolvaptan use and rate of correction of sodium levels in 67 patients. Of these, 28 were diagnosed with SIADH and 39 patients were being treated for CHF (congestive heart failure), who had sodium levels of <130mEq/L. These patients had no correction of hyponatremia with free water restriction (≤1 liter/day) for more than 24 hours. A 15mg dose of tolvaptan was given and free water restriction was discontinued to avoid overcorrection. They reported that correction exceeded 12mEq/L in 25% of patients in the SIADH cohort and in 33% of patients it exceeded 8mEq/L in 24 hours. In the CHF cohort, the numbers were 3% and 5% respectively. Also in the SIADH group, they found that lower baseline serum sodium and serum urea nitrogen levels were strongly associated with rapid correction of sodium levels (R=-0.78 and -0.76 respectively).

This is an interesting paper as it reports an increased incidence of rapid overcorrection of sodium levels with vaptans use as compared to the initial study (SALT Trial) which also looked at the effect of this medication. The SALT trial (Study of Ascending levels of tolvaptan in Hyponatremia) reported overcorrection in only 2% of their cohort. It was consistent with the other studies done in Europe where vaptans can lead to higher rate of correction. The vaptans work by increasing the free water excretion which then leads to correction of sodium levels, the amount of medication needed to inhibit the circulating ADH hormone action, in unknown.

Hence, vaptans are an extraordinary discovery in the management of hyponatremia, however, more studies are needed to better understand and predict dose-response and rate of sodium correction.

Article link:

https://doi.org/10.1053/j.ajkd.2017.12.002